Maytenus s. l. (including Gymnosporia) is a morphologically diverse genus of about 300 species that is widely distributed in the tropics and subtropics of both the Old and New Worlds. Its delimitation has been extensively debated and despite the segregation of Gymnosporia, Maytenus s. s. remains a heterogeneous, polyphyletic group. To delimit natural segregate genera we increased taxon sampling and generated sequences from two nuclear gene regions (ITS and 26S rDNA) and two plastid loci (matK and trnL-F) to analyze together with morphological characters. Both Moya and Tricerma were found to be nested within the New World Maytenus and are recognized as synonyms of Maytenus s. s.. In contrast, the three New World species of Gymnosporia are recognized as a new genus that is closely related to Gyminda. Haydenia is erected for these three species: H. gentryi, H. haberiana, and H. urbaniana. One or more previously proposed or novel genera are required to accommodate the systematically difficult African Maytenus. Putterlickia, and most likely Gloveria, are nested within Gymnosporia and should be synonymized with that genus. New binomials are required for four Chinese and one Rapan species of Gymnosporia that have been previously treated only as Maytenus: Gymnosporia austroyunnanensis, G. confertiflora, G. dongfangensis, G. guangxiensis, and G. pertinax. Austral-Pacific Maytenus are transferred to Denhamia, requiring eight new binomials: Denhamia bilocularis, D. cunninghamii, D. cupularis, D. disperma, D. fasciculiflora, D. ferdinandii, D. fournieri, and D. silvestris. Existing intrageneric classifications of Gymnosporia and Maytenus s. s. were not supported in their entirety. Gymnosporia is inferred to have had an African origin followed by dispersals to Madagascar, southeast Asia and the Austral-Pacific.